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Inhibition of the K+ conductance and Cole-Moore shift of the oncogenic Kv10.1 channel by amiodarone

  • Ion channels, receptors and transporters
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A Correction to this article was published on 16 March 2018

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Abstract

The ectopic overexpression of the voltage-dependent Eag1 (Kv10.1) K+ channel is associated with the cancerous phenotype in about 70% of human cancers and tumor cell lines. Recent reports showed that, compared with the canonical Shaker-related Kv family, Kv10.1 presents unique structural and functional properties. Herein, we report the interaction of the class III anti-arrhythmic compound amiodarone with Kv10.1. Using whole-cell patch clamp, we found that amiodarone inhibits Kv10.1 channel conductance with nanomolar affinity. Additionally, and interestingly, we also report that amiodarone inhibits the characteristic Cole-Moore shift of Eag1 channels. Our observations are interpreted considering the structural-functional characteristics of these channels. We conclude that amiodarone possibly binds with high affinity to the voltage sensor module, altering the gating of Kv10.1.

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  • 16 March 2018

    The original publication of this article contained multiple technical errors that occurred during its production and printing. These errors included sentences and paragraphs with parts missing. The Publisher regrets these mistakes.

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Acknowledgements

The authors thank Dr. Daniel Balleza for his participation in the initial phase of this work and to Mrs. Josefina Bolado of the School of Medicine, UNAM, for reviewing the English language of the manuscript.

Funding

This research was supported by PAPIIT grants IN22461-RN22461 and IN219918 grants from CONACyT Laboratorios Nacionales Consolidaci461-RN224616, for reviewin05 and 153504, and PAPIIT IN211616 and IN220916. AHG is a DGAPA-UNAM postdoctoral fellow.

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Author notes

  1. C. Barriga-Montoya, A. Huanosta-Gutiérrez and A. Reyes-Vaca contributed equally to this work.

Authors and Affiliations

  1. School of Medicine, National Autonomous University of Mexico (UNAM), Cd Universitaria 04510, Coyoacan Cd., Mexico, Mexico

    C. Barriga-Montoya, A. Huanosta-Gutiérrez, A. Reyes-Vaca & F. Gómez-Lagunas

  2. National Laboratory of Channelopathies, Institute of Cellular Physiology, UNAM, Cd Universitaria 04510, Coyoacan Cd., Mexico, Mexico

    A. Hernández-Cruz & A. Picones

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  1. C. Barriga-Montoya
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Contributions

CBM, AHG ARV, AHC, and AP made experiments and contributed to the analysis of results; FGL designed the work, made experiments, analyzed results and wrote the article.

Corresponding author

Correspondence to F. Gómez-Lagunas.

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Additional information

A correction to this article is available online at https://doi.org/10.1007/s00424-018-2131-2.

Electronic supplementary material

Supplementary Figure 1

A test for inactivation of control, unmodified, Kv10.1 channels. Non-inactivated current fraction vs. pre-pulse voltage (H616, for revi3 independent experiments carried out with non-modified, control, Kv10.1 channels. I K was evoked by a constant + 50 mV/0.1 s pulse following 1-s pre pulses from −140 to +50 mV, applied in 10 mV increments, as indicated. The non-inactivated fraction was obtained as I K(+50 mV)/I K,max, as a function of pre-pulse potential. See that at any voltage, I K drops less than 10% (for some voltages current drop is even less than 5%). Pair of pulses were applied every 20 sec. (GIF 124 kb)

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Barriga-Montoya, C., Huanosta-Gutiérrez, A., Reyes-Vaca, A. et al. Inhibition of the K+ conductance and Cole-Moore shift of the oncogenic Kv10.1 channel by amiodarone. Pflugers Arch - Eur J Physiol 470, 491–503 (2018). https://doi.org/10.1007/s00424-017-2092-x

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